Figure 2

Caveolae endocytosis helps couple regulation of differentiation signals to culture substrate elasticity. When mesenchymal stem cells are seeded on a stiff substrate with an elastic modulus similar to bone, focal adhesions and stress fibers form and nonmuscle myosin II expression increases. Cells osteogenically differentiate on the stiff substrate. The activity of nonmuscle myosin II, which promotes the assembly of focal adhesions, is required for substrate-driven differentiation. As nonmuscle myosin II expression increases in cells seeded on a stiff substrate, it may allow cells to form more focal adhesions and generate the greater force needed to deform a stiff matrix. When cells are seeded on a soft substrate, the integrin contacts with the substrate may be easily ruptured by nonmuscle myosin II-generated forces on the cell cytoskeleton. Expression of nonmyosin II remains lower and less focal adhesions and stress fibers form than in cells seeded on a stiff substrate. Activated integrins from ruptured contacts with the substrate are internalized by caveolar endocytosis. The bone morphogenetic protein receptor 1a (BMPR1a) is co-internalized and the potential for pro-osteogenic bone morphogenetic protein (BMP)-induced Smad signaling is reduced as a result. Cells neurogenically differentiate on the soft substrate. For more information, refer to [84, 85].